Anticoagulation with or without Clopidogrel after Transcatheter Aortic-Valve Implantation

Abstract

BACKGROUND The roles of anticoagulation alone or with an antiplatelet agent after transcatheter aortic-valve implantation (TAVI) have not been well studied. METHODS We performed a randomized trial of clopidogrel in patients undergoing TAVI who were receiving oral anticoagulation for appropriate indications. Patients were assigned before TAVI in a 1:1 ratio not to receive clopidogrel or to receive clopidogrel for 3 months. The two primary outcomes were all bleeding and non-procedurerelated bleeding over a period of 12 months. Procedure-related bleeding was defined as Bleeding Academic Research Consortium type 4 severe bleeding, and therefore most bleeding at the puncture site was counted as non-procedure-related. The two secondary outcomes were a composite of death from cardiovascular causes, non-procedure-related bleeding, stroke, or myocardial infarction at 12 months (secondary composite 1) and a composite of death from cardiovascular causes, ischemic stroke, or myocardial infarction (secondary composite 2), both tested for noninferiority (noninferiority margin, 7.5 percentage points) and superiority. RESULTS Bleeding occurred in 34 of the 157 patients (21.7%) receiving oral anticoagulation alone and in 54 of the 156 (34.6%) receiving oral anticoagulation plus clopidogrel (risk ratio, 0.63; 95% confidence interval [CI], 0.43 to 0.90; P = 0.01); most bleeding events were at the TAVI access site. Non-procedure-related bleeding occurred in 34 patients (21.7%) and in 53 (34.0%), respectively (risk ratio, 0.64; 95% CI, 0.44 to 0.92; P = 0.02). Most bleeding occurred in the first month and was minor. A secondary composite 1 event occurred in 49 patients (31.2%) receiving oral anticoagulation alone and in 71 (45.5%) receiving oral anticoagulation plus clopidogrel (difference, −14.3 percentage points; 95% CI for noninferiority, −25.0 to −3.6; risk ratio, 0.69; 95% CI for superiority, 0.51 to 0.92). A secondary composite 2 event occurred in 21 patients (13.4%) and in 27 (17.3%), respectively (difference, −3.9 percentage points; 95% CI for noninferiority, −11.9 to 4.0; risk ratio, 0.77; 95% CI for superiority, 0.46 to 1.31). CONCLUSIONS In patients undergoing TAVI who were receiving oral anticoagulation, the incidence of serious bleeding over a period of 1 month or 1 year was lower with oral anticoagulation alone than with oral anticoagulation plus clopidogrel. (Funded by the Netherlands Organization for Health Research and Development; POPular TAVI EU Clinical Trials Register number, 2013-003125-28; ClinicalTrials.gov number, NCT02247128.

Bleeding Complications Drive In-Hospital Mortality of Patients with Atrial Fibrillation after Transcatheter Aortic Valve Replacement

“…26 Very recently, the POPular TAVI trial compared the impact of oral anticoagulation alone with oral anticoagulation plus clopidogrel on the incidence of bleeding within 12 months after TAVR. 27 Bleeding occurred in 21.7% of patients receiving oral anticoagulation alone and in 34.6% of patients receiving oral anticoagulation plus clopidogrel. Though not tested as a specific endpoint, increased incidence of bleeding in the anticoagulation plus clopidogrel group was apparent already within the first days after TAVR while the event rates during the remaining follow-up were low and similar in both Fig.…”

“…By definition, only Bleeding Academic Research Consortium type 4 bleeding was considered as procedure-related bleeding and was observed in one patient receiving oral anticoagulation plus clopidogrel. 27 Importantly, according to the trial protocol oral anticoagulation should be continued periprocedurally, however, the choice to interrupt was left to the physician's discretion and was not reported in the trial outcomes. 27 Retrospective analyses of two smaller registries from Germany or Switzerland including 371 or 598 patients found that established anticoagulation was interrupted in approximately 50% of cases without significant difference in lifethreatening or major bleedings between patients with continued versus interrupted anticoagulation.…”

“…27 Importantly, according to the trial protocol oral anticoagulation should be continued periprocedurally, however, the choice to interrupt was left to the physician's discretion and was not reported in the trial outcomes. 27 Retrospective analyses of two smaller registries from Germany or Switzerland including 371 or 598 patients found that established anticoagulation was interrupted in approximately 50% of cases without significant difference in lifethreatening or major bleedings between patients with continued versus interrupted anticoagulation. 28,29 In contrast, in a recent prospective trial life-threatening bleeding within 30 days after TAVR occurred 4.9-fold more often in patients with AF (4.4%) compared with sinus rhythm (0.9%), although anticoagulation therapy was interrupted until 48 hours after TAVR.…”

Erkrankungen der Aorta/Herzklappen – Stichwort TAVI

“…Die additive Gabe von Clopidogrel für 3 Monate nach TAVI bei Patienten mit Indikation zur oralen Vollantikoagulation (z. B. Vorhofflimmern) wurde kürzlich in der POPular TAVI-Studie untersucht[35]. Die alleinige orale Antikoagulation ohne Clopidogrel zeigte hierbei signifikant weniger Blutungen bei gleicher Sicherheit bezüglich ischämischer Ereignisse (Schlaganfall, Myokardinfarkt und kardiovaskulärer Tod).…”

Transcatheter Aortic Valve Implantation, Atrial Fibrillation, and Bleeding: A Surprisingly Fatal Attraction

“…Of note, patients that received anticoagulation alone had a significant reduction in bleeding complications when compared with those receiving OAC plus clopidogrel for 3 months (21.7% vs. 34.6%, p ¼ 0.01). 35 Thus, results from prospective trials such as the ENVISAGE-TAVI AF and AVATAR trials are eagerly awaited and will hopefully shed more light and provide further data on an optimal antithrombotic strategy. However, similar to the PCI domain, we may be observing the limits of our current antithrombotic strategies that have inherent limitations in their ability to straddle the risk of stroke, leaflet thrombosis, and bleeding.…”